The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron.

Orally bioavailable, synthetic nonpeptide agonists (NPAs) of the glucagon-like peptide-1 receptor (GLP-1R) may offer an effective, scalable pharmacotherapy to address the metabolic disease epidemic. One of the first molecules in the emerging class of GLP-1R NPAs is orforglipron, which is in clinical development for treating type 2 diabetes and obesity. Here, we characterized the pharmacological properties of orforglipron in comparison with peptide-based GLP-1R agonists and other NPAs.

Catalytic 2-Ethylhexanoic Acid Promotes Mild Miyaura Borylations.

The Miyaura borylation of aryl and heteroaryl chlorides and bromides using a combination of potassium carbonate and 5 mol % 2-ethylhexanoic acid at 25 °C is reported. The generation of a catalytic amount of potassium 2-ethylhexanoate under these conditions avoids the need for special handling of stoichiometric quantities of hygroscopic potassium 2-ethylhexanoate during the reaction setup as well as difficulties in removing the resulting carboxylic acid during product isolation.

A General Approach to Optically Pure, α-Methyl Non-Natural Amino Acids: Enabling Unique Peptides as Drug Candidates.

An α-methyl, non-natural amino acid (NNAA) building block equipped with an alkyl halide tail that could be readily transformed into an organozinc was prepared. This single organometallic was cross-coupled to an array of heterocyclic electrophiles using the Pd-PEPPSI-IHept catalyst to produce a wide selection of optically pure α-methyl NNAAs. With these in hand, non-natural peptides are being produced for evaluation in a variety of therapeutic areas in drug discovery.

Stereoselective Synthesis of Either or 3-Azabicyclo[3.1.0]hexane-6-carboxylates by Dirhodium(II)-Catalyzed Cyclopropanation with Ethyl Diazoacetate under Low Catalyst Loadings.

Although cyclopropanation with donor/acceptor carbenes can be conducted under low catalyst loadings (<0.001 mol %), such low loading has not been generally effective for other classes of carbenes such as acceptor carbenes. In this current study, we demonstrate that ethyl diazoacetate can be effectively used in the cyclopropanation of -Boc-2,5-dihydropyrrole with dirhodium(II) catalyst loadings of 0.

Photo- and Metal-Mediated Deconstructive Approaches to Cyclic Aliphatic Amine Diversification.

Described herein are studies toward the core modification of cyclic aliphatic amines using either a riboflavin/photo-irradiation approach or Cu(I) and Ag(I) to mediate the process. Structural remodeling of cyclic amines is explored through oxidative C-N and C-C bond cleavage using peroxydisulfate (persulfate) as an oxidant. Ring-opening reactions to access linear aldehydes or carboxylic acids with flavin-derived photocatalysis or Cu salts, respectively, are demonstrated.

Conformational flexibility in carbapenem hydrolysis drives substrate specificity of the class D carbapenemase OXA-24/40.

The evolution of multidrug resistance in Acinetobacter spp. increases the risk of our best antibiotics losing their efficacy. From a clinical perspective, the carbapenem-hydrolyzing class D β-lactamase subfamily present in Acinetobacter spp.

Comparison of a Self-Care Therapeutics Course Taught in the P1 vs the P2 Year.

The objective of this study was to compare student learning outcomes, behaviors, and attitudes in a non-prescription drug and self-care therapeutics course taught in the second professional (P2) year vs the first professional (P1) year at one pharmacy school. Mean performance of students by class year on case consultations and exam scores was compared. Focus groups with student volunteers and course teaching assistants (TAs) and one-on-one interviews with a subset of instructors were conducted by an outside educational evaluation specialist to capture perceptions of student learning behaviors and attitudes.

An Audit and Comparison of pH, Measured Concentration, and Particulate Matter in Mannitol and Hypertonic Saline Solutions.

The preferred hyperosmolar therapy remains controversial. Differences in physical properties such as pH and osmolality may be important considerations in hyperosmolar agent selection. We aimed to characterize important physical properties of commercially available hyperosmolar solutions.

A commentary on ethical decision-making in the pharmacy profession and the APhA Code of Ethics.

The American Pharmacists Association Code of Ethics ("Code") was established in 1852 and has undergone 5 modifications, most recently in 1994. As point of care shifts from product to cognitive clinical service, pharmacists are expected to encounter an increasing quantity and complexity of ethical and moral dilemmas. In view of this professional transformation and current worldwide challenges, this seems an appropriate time for dialogue on a modification of the Code.

PET ligands [F]LSN3316612 and [C]LSN3316612 quantify -linked-β--acetyl-glucosamine hydrolase in the brain.

We aimed to develop effective radioligands for quantifying brain -linked-β--acetyl-glucosamine (-GlcNAc) hydrolase (OGA) using positron emission tomography in living subjects as tools for evaluating drug target engagement. Posttranslational modifications of tau, a biomarker of Alzheimer's disease, by -GlcNAc through the enzyme pair OGA and -GlcNAc transferase (OGT) are inversely related to the amounts of its insoluble hyperphosphorylated form. Increase in tau -GlcNAcylation by OGA inhibition is believed to reduce tau aggregation.

A Pilot Study Regarding Pharmacy Law Education Across Doctor of Pharmacy Programs.

To describe the features of pharmacy law education in Doctor of Pharmacy (PharmD) programs in the United States. A review of the literature found no prior published data describing the delivery of pharmacy law education across PharmD programs in the United States. Members of the Pharmacy Law Educators Subcommittee of the American Society for Pharmacy Law (ASPL) developed questions for a survey.

PET quantification of brain O-GlcNAcase with [F]LSN3316612 in healthy human volunteers.

Background: Previous studies found that [F]LSN3316612 was a promising positron emission tomography (PET) radioligand for imaging O-GlcNAcase in nonhuman primates and human volunteers. This study sought to further evaluate the suitability of [F]LSN3316612 for human clinical research.

Methods: Kinetic evaluation of [F]LSN3316612 was conducted in a combined set of baseline brain scans from 17 healthy human volunteers and test-retest imaging was conducted in 10 of these volunteers; another 6 volunteers had whole-body scans to measure radiation exposure to body organs.

Bipartite anchoring of SCREAM enforces stomatal initiation by coupling MAP kinases to SPEECHLESS.

Cell fate in eukaryotes is controlled by mitogen-activated protein kinases (MAPKs) that translate external cues into cellular responses. In plants, two MAPKs-MPK3 and MPK6-regulate diverse processes of development, environmental response and immunity. However, the mechanism that bridges these shared signalling components with a specific target remains unresolved.

Rhodium-Catalyzed Aldehyde Arylation via Formate-Mediated Transfer Hydrogenation: Beyond Metallic Reductants in Grignard/Nozaki-Hiyami-Kishi-Type Addition.

The first intermolecular carbonyl arylations via transfer hydrogenative reductive coupling are described. Using rhodium catalysts modified by BuPMe, sodium formate-mediated reductive coupling of aryl iodides with aldehydes occurs in a chemoselective fashion in the presence of protic functional groups and lower halides. This work expands the emerging paradigm of transfer hydrogenative coupling as an alternative to pre-formed carbanions or metallic reductants in C═X addition.

Cyclometalated Iridium-PhanePhos Complexes Are Active Catalysts in Enantioselective Allene-Fluoral Reductive Coupling and Related Alcohol-Mediated Carbonyl Additions That Form Acyclic Quaternary Carbon Stereocenters.

Iridium complexes modified by the chiral phosphine ligand PhanePhos catalyze the 2-propanol-mediated reductive coupling of diverse 1,1-disubstituted allenes 1a-1u with fluoral hydrate 2a to form CF-substituted secondary alcohols 3a-3u that incorporate acyclic quaternary carbon-containing stereodiads. By exploiting concentration-dependent stereoselectivity effects related to the interconversion of kinetic ( Z)- and thermodynamic ( E)-σ-allyliridium isomers, adducts 3a-3u are formed with complete levels of branched regioselectivity and high levels of anti-diastereo- and enantioselectivity. The utility of this method for construction of CF-oxetanes and CF-azetidines is illustrated by the formation of 4a and 6a, respectively.

The effect of a prescription order requirement for pharmacist-administered vaccination on herpes zoster vaccination rates.

Objective: To determine the effect of a prescription order requirement for pharmacist-administered zoster vaccination on zoster vaccination in adults aged 60+.

Methods: A 50-state law review of statutes and regulations regarding pharmacists' ability to administer the zoster vaccine with/without a prescription order was performed. States were classified as prescription order required or not required as of January 1, 2014.

A Method for Identifying and Developing Functional Group Tolerant Catalytic Reactions: Application to the Buchwald-Hartwig Amination.

Transition-metal catalysis has revolutionized organic synthesis, but difficulties can often be encountered when applied to highly functionalized molecules, such as pharmaceuticals and their precursors. This results in discovery collections that are enriched in substances possessing less desirable properties (high lipophilicity, low polar surface area). Masking groups are often employed to circumvent this problem, which is in opposition to the inherent ideality of these methods for green chemistry and atom economy.

Qualitative interviews regarding pharmacist prescribing in the community setting.

Purpose: The perceived demand for and barriers to pharmacist prescribing in the community pharmacy setting were studied.

Methods: Qualitative interviews were conducted with 19 consumers, 20 community pharmacists, and 8 reimbursement decision-makers from payer organizations between April and June 2015. Respondents were invited to participate in a daylong interview process online.

Evaluation of US Federal Legislation for Opioid Abuse: 1973-2016.

The 114th Congress (2014-2016) has received recent attention for the high number of legislative bills directed to the public health crisis in prescription opioid abuse. The US government does not have a single source for determining public policy; however, the people expect that there will be some level of efficiency and coordination between federal and state leaders to improve the nation's health. A search of the National Library of Congress database to analyze legislative bills introduced between 1973 and 2016 and which contain the term "opioid" identified 127 bills that characterize consistency and coordination with other governmental efforts in prescription opioid abuse.

Tools for "decloaking" the elephant in the room: conflict of interest, shared decision-making, and patient-centered care.

Recently, apparent failures in ethical conduct appear to have impacted the public trust of health care professionals. In particular, conflict of interest, whether actual or perceived, is hindering effective relationships between patients, clinicians, and society. Clinicians are poised to experience further damage to the goodwill and reputation of their professions if direct actions and changes to practice philosophy are not taken.

The "death" of lethal injection as we know it? The role of chemical execution in the American criminal justice system.

Several independent elements have recently combined to thrust United States capital punishment into a chaos. Corrections officials and policy makers have attempted to "humanize" capital punishment by evolving into a chemical execution process, and soften the outward appearance. Foreign policies have interrupted chemical protocols by banning key ingredients.

National evaluation of prescriber drug dispensing.

Objective: To describe the legal, professional, and consumer status of prescribers dispensing legend and over-the-counter drugs in the United States.

Methods: Legal and academic databases were searched to identify those states that permit prescribers to dispense medications to patients and any limitations on such practice. In addition, prescribers and patients-consumers were surveyed to learn about the prevalence and perceptions of such practice.